Glycemic Treatment

Control of glycemia

• 11β-HSD, 11β-hydroxysteroid dehydrogenase
• ACC, acetyl CoA carboxylase
• AICAR, 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside
• AMPK, AMP-activated protein kinase
• CVD, cardiovascular disease
• DPP, dipeptidyl peptidase
• DREAM, Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication
• FFA, free fatty acid
• GLP, glucagon-like peptide
• IGT, impaired glucose tolerance
• IR, insulin receptor
• IRS, IR substrate
• KATP, ATP-sensitive potassium
• PPAR, peroxisome proliferator–activated receptor
• TZD, thiazolidinedione
• UKPDS, U.K. Prospective Diabetes Study

This is the first of three articles dealing with the International Diabetes Federation meeting, which was held in Paris, 24–29 August 2003. Michael Stumvoll (Tübigen, Germany) gave the Minkowski lecture, discussing aspects of the control of glycemia, illustrating the “hyperbolic law of glucose control,” depicting the inverse relationship between insulin secretion and insulin sensitivity. If one adds the 2-h glucose in a three-dimensional plot, however, as insulin resistance worsens there is a progressive increase in the 2-h glucose, so that one cannot consider insulin secretion to perfectly balance the degree of insulin resistance (1). Stumvoll gave an overview of the fascinating science involved in understanding glycemia, describing the products of six genes involved in glucose homeostasis. Adiponectin is a protein released by fat cells to an extent inversely related to total body fat mass. Treatment of insulin-resistant diabetic mice with adiponectin decreases glucose levels, and in humans there is an inverse relationship between the degree of insulin resistance and the adiponectin level. Stearoyl-CoA desaturase regulates tissue lipid synthesis and is involved in the metabolism of stearate to oleate. In liver, inhibition of this enzyme prevents hepatic steatosis in leptin-deficient animals, and the oleate-to-stearate ratio on liver biopsy is inversely related to the insulin sensitivity. The insulin receptor (IR) substrate (IRS)1 modulates insulin secretion, with β-cell overexpression of normal IRS1 increasing insulin secretion, whereas overexpression of an abnormal IRS1 decreases insulin secretion by these cells. In humans, those with the Gly972Arg IRS1 polymorphism have shown a decrease in both the first- and second-phase insulin secretory response to intravenous glucose (2). CEACAM1 (CEA-related cell adhesion molecule 1) regulates a pathway responsible for IR internalization, and abnormality causes diabetes. CEACAM1 causes receptor-mediated hepatic insulin endocytosis and degradation in a phosphorylation-dependent manner (3). The liver clears approximately half of the insulin molecules …